Menopause is a normal natural aging event that affects all women. Menopause can be defined as the cessation of ovulation and menses for at least 12 months with no obvious pathological cause. The typical age for menopause is 51 years and it is estimated that in the US today (2010 Census) there are more than 53 million women who are of post-menopausal age (50+ years). Additional women fall into the post-menopausal category by virtue of a total hysterectomy (removal of uterus and both ovaries). Associated with post-menopause is a dramatic decline in circulating estradiol to less than 10% of the level that is typical during a woman's reproductive years. The reduced estrogen sets in motion major anatomic changes leading to unique symptoms and quality of life issues.
While decreasing estrogen has been reported to have a systemic effect on a woman's body, skin, and hair, the effect is also seen on the urogenital area, being diagnosed as vaginal atrophy or VA. VA assessment may require the insertion of a speculum into the woman's vagina. Subjective assessments are made that include loss of hymenal ruggae, presence of patulousness of the urethra, a telescoping vestibule, presence of petechiae in the vagina, and loss of elasticity that is digitally (finger) diagnosed at the introitus. The predominant symptoms reported by women include a feeling of vaginal dryness, pain with sexual penetration, bleeding with sexual penetration, vaginal itch, and genital skin itch; among others.
Objective measures and testing methods for VA rely on testing in the vagina at the mucosal surface. The hymen is a membrane that surrounds or partially covers the external vaginal opening (the tissue surrounding this opening can be referred to as the hymenal ring). The hymen is the limit between the internal and external genitalia. It consists of a thin fibrous membrane lining the lower vagina, covered on its external surface by a keratinized stratified squamous epithelium and on the internal surface by nonkeratinizing stratified squamous epithelium with glycogen (like the vaginal epithelium). For many women with VA, the hymen may constrict and lose elasticity thereby making it difficult or unpleasant to objectively be tested for VA. The tissue associated with the vaginal opening is also referred to as the introitus. Objective measures of VA are largely restricted to vaginal pH (typically requiring a speculum to create adequate access) where a pH of greater than or equal to 5.5 has been classified as a sign of VA. Vaginal scraping of the epithelial lining (also requiring a speculum insertion into the vagina) can be analyzed for the relative abundance of mature cells (called vaginal maturation index or VMI). However, the relationship between the VMI to VA varies among clinicians, and the variation can be quite broad. Similarly there is no clear relationship between a woman's symptomology and clinical assessment, or objective measures of vaginal pH.
Another potential objective method for diagnosing VA and the effect of a treatment might include the collection of a vaginal biopsy for transcriptional profiling. Obtaining a vaginal biopsy is quite difficult, requiring the use of a speculum. Further, one cannot be precise as to where the biopsy is derived nor ensure uniform properties of the biopsy. For example, differences in biopsy thickness can bias data derived from the dermis.
Further, with the exception of vaginal pH, all the other methods are subjective and not reliable. Another problem is that all the vaginal procedures such as the subjective vaginal atrophy grading or collecting vaginal pH or collecting vaginal scrapings for the VMI require the insertion of a speculum into the vagina. This procedure can be quite painful especially among women who suffer from VA. While the speculum can be lubricated (typically with commercial ultrasound gel) for easier insertion, this can compromise the collection of pH and VMI. The pain caused by the insertion of a speculum may influence whether a woman decides to seek diagnosis and treatment for VA.
As such there is a need for VA diagnostic methods and methods to assess the potential efficacy of treatments for VA that do not rely on the use of a speculum, sampling of vaginal tissue, and reduce the level of subjectivity by using a quantitative and objective method.